Erratum to: System Dynamics Evaluation of Climate Change Adaptation Strategies for Water Resources Management in Central Iran

The Zayandeh-Rud River basin, Iran, is projected to face spatiotemporally heterogeneous temperature increase and precipitation reduction that will decrease water supply by mid-century. With projected increase (0.70–1.03 °C) in spring temperature and reduction (6– 55%) in winter precipitation, the upper Zayandeh-Rud sub-basin, the main source of renewable water supply, will likely become warmer and drier. In the lower sub-basin, 1.1–1.5 °C increase in temperature and 11–31% decrease in annual precipitation are likely. A system dynamics model was used to analyze adaptation strategies taking into account feedbacks between water resources development and biophysical and socioeconomic sub-systems. Results suggest that infrastructural improvements, rigorous water demand management (e.g., replacing high water demand crops such as rice, corn, and alfalfa), and ecosystem-based regulatory prioritization, complemented by supply augmentation can temporarily alleviate water stress in a basin that is essentially governed by the Limits to Growth archetyp

Phosphopantetheinyl transferase (Ppt)-mediated biosynthesis of lysine, but not siderophores or DHN melanin, is required for virulence of Zymoseptoria tritici on wheat

Zymoseptoria tritici is the causal agent of Septoria tritici blotch (STB) disease of wheat. Z. tritici is an apoplastic fungal pathogen, which does not penetrate plant cells at any stage of infection, and has a long initial period of symptomless leaf colonisation. During this phase it is unclear to what extent the fungus can access host plant nutrients or communicate with plant cells. Several important primary and secondary metabolite pathways in fungi are regulated by the post-translational activator phosphopantetheinyl transferase (Ppt) which provides an essential co-factor for lysine biosynthesis and the activities of non-ribosomal peptide synthases (NRPS) and polyketide synthases (PKS). To investigate the relative importance of lysine biosynthesis, NRPS-based siderophore production and PKS-based DHN melanin biosynthesis, we generated deletion mutants of ZtPpt. The ?ZtPpt strains were auxotrophic for lysine and iron, non-melanised and non-pathogenic on wheat. Deletion of the three target genes likely affected by ZtPpt loss of function (Aar- lysine; Nrps1-siderophore and Pks1- melanin), highlighted that lysine auxotrophy was the main contributing factor for loss of virulence, with no reduction caused by loss of siderophore production or melanisation. This reveals Ppt, and the lysine biosynthesis pathway, as potential targets for fungicides effective against Z. tritici

Intestinal lesions in dogs with acute hemorrhagic diarrhea syndrome associated with netF-positive Clostridium perfringens type A

Acute hemorrhagic diarrhea syndrome (AHDS), formerly named canine hemorrhagic gastroenteritis, is one of the most common causes of acute hemorrhagic diarrhea in dogs, and is characterized by acute onset of diarrhea, vomiting, and hemoconcentration. To date, histologic examinations have been limited to postmortem specimens of only a few dogs with AHDS. Thus, the aim of our study was to describe in detail the distribution, character, and grade of microscopic lesions, and to investigate the etiology of AHDS. Our study comprised 10 dogs with AHDS and 9 control dogs of various breeds, age, and sex. Endoscopic biopsies of the gastrointestinal tract were taken and examined histologically (H&E, Giemsa), immunohistochemically (Clostridium spp., parvovirus), and bacteriologically. The main findings were acute necrotizing and neutrophilic enterocolitis (9 of 10) with histologic detection of clostridia-like, gram-positive bacteria on the necrotic mucosal surface (9 of 10). Clostridium perfringens isolated from the duodenum was identified as type A (5 of 5) by multiplex PCR (5 of 5). In addition, each of the 5 genotyped isolates encoded the pore-forming toxin netF. Clostridium spp. (not C. perfringens) were cultured from duodenal biopsies in 2 of 9 control dogs. These findings suggest that the pore-forming netF toxin is responsible for the necrotizing lesions in the intestines of a significant proportion of dogs with AHDS. Given that the stomach was not involved in the process, the term acute hemorrhagic diarrhea syndrome seems more appropriate than the frequently used term hemorrhagic gastroenteritis

DNA-Dependent Protein Kinase Inhibits AID-Induced Antibody Gene Conversion

Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(D)J regions, subsequent excision of the deaminated bases by uracil-DNA glycosylase, or by mismatch repair, leads to further point mutation or gene conversion, depending on the species. In Ig S regions, nicking at the abasic sites produced by AID and uracil-DNA glycosylases results in staggered double-strand breaks, whose repair by nonhomologous end joining mediates Ig class switching. We have tested whether nonhomologous end joining also plays a role in V(D)J hypermutation using chicken DT40 cells deficient for Ku70 or the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inactivation of the Ku70 or DNA-PKcs genes in DT40 cells elevated the rate of AID-induced gene conversion as much as 5-fold. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion

Liver cancer mortality at national and provincial levels in Iran between 1990 and 2015: A meta regression analysis

Background: Liver cancer is a highly lethal cancer with 5 year survival rate of about 18. This cancer is a leading cause of death in many countries. As there is not a comprehensive population base study on liver cancer mortality rates by cause in national and provincial level in Iran. We aimed to estimate the liver cancer mortality rate, its patterns, and temporal trends during 26 years by sex, age, geographical distribution, and cause. Methods: We used the Iranian death registration system (DRS), in addition to demographic and statistical methods, to address the incompleteness and misclassification and uncertainty of death registration system to estimate annual liver cancer mortality rate. Direct age standardized approach was applied using Iran national population 2015 as a standard population to facilitate the comparison between the provinces. Results: Liver cancer age standardized mortality rate in Iran increased by more than four times from 1.18 (95 uncertainty interval; 0.86 to 1.61) deaths per 100,000 person in 1990 to 5.66 (95 uncertainty interval; 4.20 to 7.63) deaths per 100,000 person in 2015. Male to female age adjusted mortality ratio changed from 0.87 to 1.82 during the 26 years of the study. With increasing age, liver cancer mortality rate increased in both sex and all provinces. At provincial level, the province with highest mortality rate have 2.96 times greater rate compare to the lowest. Generally, about 71 of mortality at national level is due to hepatitis B and C infection. Conclusions: In order to reduce liver cancer mortality rate, it is recommended to control main risk factors including chronic hepatitis infections. Because of the growing rate of mortality from liver cancer, augmenting life expectancy, and increasing number of the elderly in Iran, policy makers are more expected to adopt measures including hepatitis B vaccination or hepatitis C treatment. © 2018, Hepatitis Monthly

Liver cancer mortality at national and provincial levels in Iran between 1990 and 2015: A meta regression analysis

Background: Liver cancer is a highly lethal cancer with 5 year survival rate of about 18. This cancer is a leading cause of death in many countries. As there is not a comprehensive population base study on liver cancer mortality rates by cause in national and provincial level in Iran. We aimed to estimate the liver cancer mortality rate, its patterns, and temporal trends during 26 years by sex, age, geographical distribution, and cause. Methods: We used the Iranian death registration system (DRS), in addition to demographic and statistical methods, to address the incompleteness and misclassification and uncertainty of death registration system to estimate annual liver cancer mortality rate. Direct age standardized approach was applied using Iran national population 2015 as a standard population to facilitate the comparison between the provinces. Results: Liver cancer age standardized mortality rate in Iran increased by more than four times from 1.18 (95 uncertainty interval; 0.86 to 1.61) deaths per 100,000 person in 1990 to 5.66 (95 uncertainty interval; 4.20 to 7.63) deaths per 100,000 person in 2015. Male to female age adjusted mortality ratio changed from 0.87 to 1.82 during the 26 years of the study. With increasing age, liver cancer mortality rate increased in both sex and all provinces. At provincial level, the province with highest mortality rate have 2.96 times greater rate compare to the lowest. Generally, about 71 of mortality at national level is due to hepatitis B and C infection. Conclusions: In order to reduce liver cancer mortality rate, it is recommended to control main risk factors including chronic hepatitis infections. Because of the growing rate of mortality from liver cancer, augmenting life expectancy, and increasing number of the elderly in Iran, policy makers are more expected to adopt measures including hepatitis B vaccination or hepatitis C treatment. © 2018, Hepatitis Monthly

BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells

Arsenic exposure constitutes one of the most widespread environmental carcinogens, and is associated with increased risk of many different types of cancers. Here we report that arsenite (As[III]) can induce both replication-dependent DNA double-strand breaks (DSB) and homologous recombination (HR) at doses as low as 5 µM (0.65 mg/l), which are within the typical doses often found in drinking water in contaminated areas. We show that the production of DSBs is dependent on active replication and is likely to be the result of conversion of a DNA single-strand break (SSB) into a toxic DSB when encountered by a replication fork. We demonstrate that HR is required for the repair of these breaks and show that a functional HR pathway protects against As[III]-induced cytotoxicity. In addition, BRCA2-deficient cells are sensitive to As[III] and we suggest that As[III] could be exploited as a therapy for HR-deficient tumours such as BRCA1 and BRCA2 mutated breast and ovarian cancers